Grant: Team Grant: Terry Fox New Frontiers Program in Cancer (LOI)

Cancer is a complex and challenging disease to study, partly because many common cancers are not defined by a single driving event. Rather, a constellation of many different genetic changes can occur in these cancers, only some of which will be present in any particular patient. It follows that common cancers are characterized by extreme heterogeneity both molecularly and clinically. The situation is very different in many rarer tumours which often share a single, identical defect that translates into uniform clinical presentation and prognosis. Identification of the defects responsible for rare tumours is beneficial for affected patients, but less obviously, the study of rare tumours has historically led to insights into basic cellular processes which has advanced cancer research overall. We will take advantage of this strategy to study a series of 20 rare tumour types that have unknown underlying defects with the aim of gaining understanding not only about these diseases but about cancer in general. As our first project we will use new DNA sequencing technology to analyse the entire suite of expressed genes in these tumours with the hopes of identifying the genetic changes that are causing these rare tumours. Our second project will exploit new advances in microfluidics to enable genomic analysis of very small amounts of sample and single cells, and will also develop new genomic tests that will be used for clinical diagnostics. Our final three projects will use the sequencing data and newly developed technologies generated in Project 1 and 2 to explore if specific molecular changes in these cancers affect RNA editing, cancer cell epigenetics, and changes to gene expression respectively. This work will lead both to direct improvements in the diagnosis and ultimately treatment for Canadians who have rare cancers and insights into the general mechanisms relevant to common cancers.